Urinary incominence (UI) is a common problem in middle aged and older women that substantiMly impacts quality of life, increases caregiver burden and risk of institutionalization, and results in biUiom of dollars in health care expenditures annuaUy. Our studies, and those of other investigators, have identified several established and potential risk factors for incominence, including childbirth, hormone use, diabetes, obesity and surgery, urinary tract infections, pelvic organ prolapse, and physical activity. Dr. Lue, another UCSF SCOR investigator, have used animal models to investigate several major risk factors identified epidemiologically, including vaginal birth (normal and traumatic), obesity, hysterectomy, menopause, and oral estrogen therapy. In vitro studies of hormone receptors using tissue cultures from the lower urinary tract of laboratory animals and humans by investigators at UCSF and elsewhere have advanced our understanding of the complex interaction between exogenous and endogenous hormones and urogenital physiology. The primary objective for the proposed study is to increase our understanding of risk factors for incontinence by identifying risk factors for incident UI, assessing biologic markers as risk factors for prevalent UI, and integratmg our investigations with laboratory investigation in this area. We will accomplish this by prospectively following a population-based, ethically diverse cohort of 2100 middle-aged and older women over 5 years to: (1)determine the incidence of and risk factors for new urinary incontinence; (2) determine the incidence of and risk factors for major changes in incominence frequency; and (3) investigate serum 17-13-cstradiol and progesterone as risk factors for prevalent incontinence. A major strength of this study is our retrospective cohort of 2100 women for who we have detailed data on lifetime reproductive events from abstraction of up to 50 years of medical records, detailed interviews, and linkage to excellent pharmacy, laboratory, outpatient and hospital databases. Another strength is our established relationships with laboratory investigators in this area. Combining a prospective epidemiologic study of our unique cohort with laboratory studies will help translate findings into new preventive and theraocutic aooroaches to reduce the individual and social burden of urinary incontinence.